“I thought it was just a little limp…” Part 4: Chemotherapy options for canine osteosarcoma

It’s been two weeks since Duffy’s amputation surgery, and he’s coming in to see me for a check-up, and a final discussion on what our plan for his future will be. I anxiously awaited his arrival to my examination area, recalling how when he went home two days after surgery he seemed slightly sluggish with some impressive swelling and redness over his incision site.
Duffy definitely showed some difficulty rising from recumbency and even slipped once on the tiled floor of the waiting room while being discharged from the hospital.
Before I actually saw Duffy, I heard him — or rather I heard the rapid footsteps of one of our oncology technicians pattering down the hallway, the distinct jingling of tags swinging against a collar, and the heavy panting (which I truthfully could not distinguish as being canine or human in origin). The door to my examination area opened and in bounded a massive storm of golden fur and wet slobbery kisses attached to a giant pink tongue.
“Duffy’s doing great at home,” the technician stated as she adjusted her now lopsided ponytail while simultaneously catching her breath. “I think they are leaning towards chemotherapy!”
The fact that Duffy was bouncing around the room on three legs without hesitation did not surprise me at all. Most dogs recover from amputation surgery within a short period of time. Dogs who are overweight or have significant orthopedic disease may not be quite as agile as Duffy at this time point, and can benefit from post-operative physical therapy to strengthen other muscles and joints.
As an alternative to amputation for dogs with tumors located in the lowest portions of the radius or ulna (bones of the forelimb), metacarpal or metatarsal bones (longer bones of the paws), or digits (toes), owners also have the option of a “limb-sparing” surgery. In this surgery, the affected portion of the bone is removed, leaving the limb in place.
These can be technically challenging surgeries and complications can arise, including post-operative infections and regrowth if any portion of the tumor is left behind. Owners should really only consider this form of surgery if they are willing to commit to treating their pet with chemotherapy afterwards.
I typically discuss two main chemotherapy options for dogs with osteosarcoma: pursuing injectable chemotherapy versus pursuing treatment with a newer form of treatment called metronomic chemotherapy.
Injectable chemotherapy is the most well studied form of treatment for dogs with osteosarcoma. There are three drugs that are effective for this disease: doxorubicin, cisplatin, and carboplatin. Numerically, the outcomes are similar for each drug, though it is important to point out that no one has adequately performed the perfect study comparing the efficacy of each drug in a “head to head” fashion.
We generally say the prognosis for dogs treated with amputation alone is about 4-5 months. With additional chemotherapy with doxorubicin, cisplatin, or carboplatin, survival is extended to about 12 months, with approximately 10-15 percent of dogs surviving two years.
Doxorubicin is an intravenous drug given once every three weeks for a total of five treatments. This drug is usually well tolerated but has a moderate chance of causing upset stomach signs. There is a risk for toxicity to the heart; a problem seen when dogs receive more than six lifetime dosages, which is one of the main reasons we stop at five treatments.
Cisplatin is an intravenous form of chemotherapy administered once every three weeks for a total of four treatments. Of the three drugs, it is the one most likely to cause side effects in dogs. It is an example of a chemotherapy drug that can immediately cause nausea and vomiting, so it must be administered with anti-nausea medications. This drug can also be directly toxic to the kidneys, so it must be administered with an all-day intravenous fluid diuresis.
Carboplatin is also an intravenous drug given once every 3-4 weeks for a total of five treatments. Side effects are uncommon, but it can definitely cause lowered white blood cell counts.
Metronomic chemotherapy is also known as anti-angiogensis therapy. The idea behind this form of treatment is in order for tumor cells to grow, multiply, and spread, they need to grow their own blood supply. If this process can be inhibited, then it may be possible for dogs to live with tumor cells in their body, but the cells will not grow, or may grow at a slower rate.
This form of treatment is becoming a popular treatment options for pets with cancer, mainly because these are oral formulations of drugs owners can administer at home. There is limited research in veterinary medicine supporting the efficacy of this method of treatment, however a few small studies showed potential benefit for dogs with cancers other than osteosarcoma.
I discuss metronomic chemotherapy as a “stand-alone” option, but recommend the injectable protocols initially, and then consider stating a dog on metronomic treatment once the finish their protocol. More on this form of therapy will follow in a future article.
I completed my exam of Duffy and headed in to talk with his owners. We went over the pros and cons of treatment with chemotherapy versus starting Duffy on a close monitoring program. Ultimately, they elected to start treatment with carboplatin, knowing we were ideally committing to completing all five treatments, but knowing we were going to take things day by day.
Their fears were the same as any owner starting treatment with chemotherapy, but they knew they wanted to give Duffy every available chance for long-term survival.
Duffy received his first chemotherapy as planned, and is currently feeling great at home. He’s chasing squirrels, stealing cookies from the table, and acting generally “normal” at home.
From my perspective, Duffy is a true success story. He may not be breaking any records, but I feel confident he will continue to do well and share his happiness with his family for a long time.

“I thought it was just a little limp…” Part 3: Palliative options for canine osteosarcoma

Thus far I’ve discussed various methods we use to diagnose dogs with osteosarcoma and the staging tests for canine osteosarcoma. In the following two articles I will describe palliative and definitive treatment options for this disease, and their respective prognoses.

To review, osteosarcoma is an aggressive form of bone cancer in dogs. Most tumors arise within weight-bearing bones, and the majority of dogs are presented to their veterinarians because of lameness. In most cases, the recommendation will be to amputate the affected limb, and with this surgery, the expected prognosis is about 4-5 months.

The short survival time is because this cancer usually has already spread to distant sites in the body before we are able to detect it. Amputating a limb without further therapy is considered palliative treatment, but remains the most effective way to remove the source of pain for the patient.

Many owners fear amputation, as they believe their dog will be unable to ambulate on three limbs, or that the loss of a limb will somehow alter their dog’s personality/demeanor. In my experience, this is exceedingly rare.

A very good resource of information about amputation is Tripawds, where the motto is “It’s better to hop on three legs than limp on four.” Here, owners of three-legged pets provide a fantastic support network for each other and for owners considering surgery. One can find a group of “peers” to bounce questions off of and read personal experiences on individual blog pages and forums. I also direct owners to search “Three-legged dogs” on youtube, as there are thousands of videos of dogs racing around after amputation, helping to support the notion that amputation is neither cruel nor debilitating.

For cases where amputation is not an option, or when owners will not consider this procedure, alternative palliative measures can be attempted as a means to reduce pain.

In human cancer terms, palliative treatments are designed to alleviate clinical signs related to the tumor(s), but are not necessarily expected to extend that patient’s lifespan.

In veterinary medicine, if palliative options are successful in controlling pain related to cancer, patients will often live longer than they would if their signs were not controlled, simply because their quality of life is vastly improved and euthanasia can be delayed. Survival may only be extended by a few weeks to months, but for many owners this is exactly what they need to come to terms with the diagnosis and enjoy good quality time with their pets.

One very effective form of palliative treatment for dogs with osteosarcoma is radiation therapy. During radiation therapy, high-energy beams of radiation are applied to a tumor from an external source. Most facilities treating dogs with radiation use a linear accelerator machine. Treatment protocols vary, but may consist of one treatment a week for 4-6 weeks, or consecutive daily treatments for 2-5 days. Studies indicate around 70-90 percent of dogs will show improvement in their pain scores, with most dogs showing improvement with just one treatment.

Dogs can develop fairly significant localized skin reactions with this form of radiation, with hair loss, ulceration, scabbing, and swelling seen in many cases. Palliative radiation therapy also causes increased susceptibility to fracturing an already weakened bone. This is likely from a combination of activity and stress on the limb because the pet feels better, and because the radiation therapy could inherently cause damage to the bone.

Stereotactic radiation therapy is a newer form of radiation available at some university and referral hospitals. This form of radiation is more localized for treating the tumor while sparing the normal tissue surrounding the tumor, therefore less likely to cause some of the side effects listed above.

Bisphosphonates are intravenous or oral medications used to treat bone pain in dogs. Drugs in this class were developed to prevent osteoporosis in post-menopausal women. They work to inhibit bone resorption, which is one of the main sources of pain in bone cancer. These medications are extremely well tolerated, with minimal to no side effects, and when used as a sole treatment options, are successful in relieving pain in 40 percent of patients.

Oral medications are the mainstay of palliative treatment for dogs with osteosarcoma. Often we are prescribing a combination of pain medications that include non-steroidal anti-inflammatories, along with strong opioid or opioid-like drugs and neuropathic pain inhibitors. Long-acting analgesic nerve blocks can also be used.

Some veterinarians advocate the use of acupuncture, homeopathic remedies, and/or physical therapy for treating bone pain. I do not have personal experience with these options, but am always open to discussing pros and cons with owners.

I recommend a combination of all of the above-mentioned options for dogs with osteosarcoma, as I truly believe a multi-modality approach is most successful. Statistics will argue that dogs treated palliatively do not live longer than dogs that undergo surgical amputation alone (about 4-5 months). However, in my clinical experience the 4-5 months for dogs with adequate pain control are far more enjoyable than for those whose pain we cannot control.

Focusing back on our patient Duffy, I discussed palliative options with his owners, especially in light of the concern for the small lesion seen within one of his lung lobes.

As with most owners, their main concern was making sure Duffy remained pain-free for as long as possible. Although they weren’t quite sure they were ready to commit to chemotherapy after surgery, they were willing to take the risk in the face of possible metastatic disease and elected to move forward with amputation of his affected limb. We were able to perform surgery the very next day, making the time from when I met Duffy to his recovery from amputation (and beginning of time pain-free) less than three days.

Next week, in the final article in this series, I will discuss the chemotherapy options for treating dogs with osteosarcoma, and what Duffy’s owners ultimately elected for his long-term treatment plan.

“I thought it was just a little little limp”, Part 2…

Last week I introduced you to Duffy, an older Golden retriever, whose seemingly simple limp turned out to be a harbinger for the devastating diagnosis of osteosarcoma. This week I want to go over some of the available staging tests designed to look for spread of this type of cancer, as well as provide my clinical insight into their value and utility.
The recommended treatment of choice for dogs with osteosarcoma of a weight-bearing bone is amputation of the affected limb. In only very specific cases, we may consider localized excision of the affected portion of the bone without pursuing an amputation (i.e., limb-sparing surgery). More information on this procedure will follow in a subsequent article.

Osteosarcoma is a highly metastatic tumor. The most common locations where the cancer will spread to are the lungs and to other bones. At the time of diagnosis, greater than 90 percent of dogs will test negative for spread of disease. Yet even with immediate removal of the tumor, most dogs will develop metastatic tumors within a few short months after surgery. This indicates that the cancer already spread before the primary tumor was removed, but existed at a level below our ability to detect it. The average lifespan is only expected to be about 4-5 months with amputation alone.

Given the propensity for this cancer to spread to the lungs and other bones, historically we used radiographs (X-rays) of the lungs along with our physical exam findings as the main ways to assess for spread. There are some limitations to these diagnostic tests though; in order for a metastatic tumor to be visible on a radiograph, it must be about 1cm3 in size, which is estimated to be about 1 billion cancer cells. It doesn’t take a medical degree to know that’s a huge amount of cancer cells. We also know animals do not show signs of pain the same way people do, and physical exams can be notoriously insensitive for picking up the discomfort associated with a metastatic tumor within another bone.
Advanced diagnostic tests with increased sensitivity for detecting spread of osteosarcoma tumors are now more readily available. We now recommend a thoracic CT scan as this imaging modality is superior to radiographs for picking up smaller tumors within the lungs and are also better at localizing tumors to specific portions of this tissue. We also can perform nuclear scintigraphy, which is a diagnostic test useful for picking up tumors in other skeletal bones.
CT scans and nuclear scintigraphy are wonderful testing options, but tend to be limited in their availability, are expensive, and have the downside of requiring heavy sedation and/or general anesthesia. They also have their own particular false positive and false negative rates and are qualitative tests, meaning they rely on human interpretation and operator error, which sometimes contributes to confusing results.
Some veterinarians recommend performing abdominal ultrasounds as a screening test on dogs with bone tumors. The odds of a bone tumor spreading to an internal organ would be exceedingly low, but the odds of an abdominal ultrasound picking up one or more abnormalities of indeterminate significance would be moderate. Typically this leads to further tests, which themselves may or may not be conclusive. All the while we have a painful patient and confused and emotional owners who are simply looking for the right thing to do for their dog.
Advanced testing options are great, but when I discuss their utility with owners, I really try to put the focus on determining what their goal is for their dog. We have to ask ourselves what we will do with the results of the test before performing it, and will these results alter the recommended treatment plan?
Dogs with osteosarcoma are painful, and although there are several available palliative treatment options, each falls considerably short in their ability to control pain when compared to amputation. If a CT scan shows hundreds of tiny tumors throughout all lung lobes, I agree the prognosis for long-term survival is poor. But do we not consider amputation of that pet’s limb to control pain while they are still asymptomatic for spread? What if the scan shows two tumors, or just a possible tumor? How do we decide the right answer?
In my opinion, whether metastases are detected or not at the time of diagnosis, surgical amputation of the affected limb in an otherwise asymptomatic dog is something I will recommend in nearly all cases. I didn’t always feel this way, and this stance is something I’ve adopted through my years of working as an oncologist trying to medically manage the discomfort of dogs with bone tumors.
Of course, not every owner elects for amputation, and not every dog is a candidate for this surgery (e.g., they may have severely debilitating orthopedic or degenerative neurological diseases that hamper their ability to ambulate even with four limbs). In those cases, we have several options for palliation of pain, each with it’s own varying success rates, which will be the subject of next week’s article.
I discussed the option of pursuing advanced testing with Duffy’s owners and they elected to pursue the thoracic CT scan, bone scintigraphy, and the abdominal ultrasound, which fortunately were all negative for any spread or intercurrent disease, with the exception of a pesky suspicious 4mm nodule in one of his left lung lobes.
And thus began the discussion of amputation versus palliative care for Duffy.
To be continued…

“I thought it was just a little limp.” When a diagnosis of lameness leads to something more concerning…

Duffy’s owners noted he was limping on his right front leg a few weeks ago. They didn’t give it much consideration at the time. It wasn’t unusual for this handsome and active 9 year-old Golden retriever to tweak a muscle once in a while, and after a few days of rest and prescription anti-inflammatory medication, Duffy was feeling much better.

 

The lameness returned about 10 days later, and this time they noticed a swelling above Duffy’s carpus (wrist) on the same limb. They recognized this wasn’t just a sore muscle and they made an appointment with his primary veterinarian the next day.

 

Duffy’s vet performed radiographs (x-rays) of the swelling over his carpus. The images revealed near complete destruction of the distal (lowest) part of the radius (weight-bearing bone of the forelimb) with a significant amount of swelling and also some new bone formation. All of these signs unfortunately pointed towards the high likelihood Duffy had bone cancer. Duffy’s doctor recommended they come talk to me about different options available for obtaining a definitive diagnosis and also to learn about some potential treatment options.

 

I met Duffy and his worried owners soon after. I agreed with Duffy’s vet, and discussed most likely he had a specific type of bone cancer called osteosarcoma. This very aggressive tumor causes significant pain for affected dogs, and is also highly metastatic, meaning there was a high chance tumor cells had already spread to distant sites in Duffy’s body. The most common sites of spread would be the lungs and other bones.

 

I talked with Duffy’s owners about tests we could perform to be certain of my concern and also how we could look for any spread of his cancer. The “gold-standard” test for diagnosing bone cancer in dogs is a biopsy, where small pieces of the affected bone are removed with a surgical procedure under general anesthesia.

 

Although a biopsy is likely to provide an accurate diagnosis, there are some downsides to the procedure. The turn around time for biopsy samples can be as long as week or more, and during that time pets are still painful, and there is a risk (albeit low) for causing a fracture of an already weakened bone. There is also a small risk of infection and bleeding, and if not planned correctly, seeding tumor cells into the surrounding connective tissue.

 

For dogs with suspected bone cancer, I typically recommend we start with an ultrasound guided fine needle aspirate of the lesion itself. This is a relatively straightforward procedure that is performed under light sedation. A medium-sized needle is inserted into the affected bone and cells can be extracted and evaluated under a microscope by a trained cytopathologist.   The major pro of this test is the rapid turn around time (within 24-48 hours in most cases), and the risk of inducing a fracture is minimal.

 

The fine needle aspirate test is very good for obtaining a diagnosis of “cancer vs. not cancer.” Results typically indicate either sarcoma (cancer) or reactive bone (no obvious cancer). Sarcomas are tumors of connective tissue, and bone is an example of one of many types of connective tissue in the body.

 

When it comes to bone sarcomas, there are several types we commonly see within bones. As stated above, osteosarcoma would be the most common type, followed by chondrosarcoma, fibrosarcoma, and hemangiosarcoma. Other primary bone tumors include histiocytic sarcoma and multilobular osteochondrosarcoma.

 

The reason an aspirate lacks the specificity to determine the subtype of sarcoma is because with this procedure we are just extracting individual cells, whereas a biopsy sample will obtain not only tumor cells, but other elements of the bone itself that help a pathologist determine the exact nature of the tumor.

 

If an aspirate sample returns positive for sarcoma, an additional test (alkaline phosphatase stain) can be performed to rule in or rule out osteosarcoma. I urge owners to start with an aspirate first as I find it the most rapid way to obtain a diagnosis with minimal risk to the patient.

 

I discussed this with Duffy’s owners and they elected to move forward with the radiographs of his lungs and the fine needle aspirate procedure. As expected Duffy handled the procedure perfectly, with no complications. We added some stronger pain medications to his at home anti-inflammatory treatment and he left that day still limping, but carefree and happy, not understanding his owner’s worry at all.

 

Two days later, late in the evening after finishing my appointments, I sat down to call Duffy’s owners. On a conference call with both owners eagerly awaiting my words, I sadly relayed the test results confirmed our suspicions: Duffy had osteosarcoma.

 

I’m not often the one breaking the news of a diagnosis of cancer to owners, but when I do I’ve noticed there are several typical reactions. Some owners will become angry and lash out while others are too upset to speak.   Duffy’s owners fell into the “strong but silent” type, not really showing much emotion, stoically listening to my words with a bit of detachment and hint of skepticism. They asked what the next step would be, and I told them I recommended they schedule an amputation of Duffy’s affected limb as soon as possible.

 

The subtle short intake of breath by both owners was barely audible through the phone, yet I immediately knew its significance. In it, I detected the fear of the prospect of surgery and what it would mean for Duffy to live the remainder of his life as a three-legged dog. I’ve had this discussion with owners numerous times before, and I knew I was about to embark on a lengthy and emotionally driven conversation.

 

I literally kicked off my heels and put my feet up on my desk and stated, “Try not to panic. Let me tell you what you can expect…”

 

Stay tuned to learn about what Duffy’s owners decided and learn more about therapeutic options and the prognosis dog with osteosarcoma.